Lambda holin family

The Lambda Holin S (λ Holin) Family (TC# 1.E.2) is a group of integral membrane transporter proteins belonging to the Holin Superfamily III.[1] Members of this family generally consist of the characteristic three transmembrane segments (TMSs) and are of 110 amino acyl residues (aas) in length, on average. A representative list of members belonging to this family can be found in the Transporter Classification Database.

Lambda Holin S[edit]

Lambda holin S (Lysis protein S of phage lambda, holin S105; TC# 1.E.2.1.1) is the prototype for class I holins. It has 3 TMSs with the N-terminus in the periplasm and the C-terminus in the cytoplasm. Its 107 codon sequence encodes two proteins with opposing functions, the holin, S105, and the holin inhibitor, S107. The latter protein, S107, is a 2-amino acid extension of the former protein, S105, due to a different translational initiation start site (M1-K2-M3 vs. M3). A cationic amino acid at position 2 is largely responsible for the inhibiting effect of S107. The ratio of S105 to S107 influences the timing of phage lambda-induced cell lysis. The highly hydrophilic C-terminal domains of holins (e.g., lambda S105) have been shown to be localized cytoplasmically and serve as regulatory domains. Like the N-terminal 2 amino acid extension in S107, they influence the timing of lysis by a charge dependent mechanism.[2][3][4]

Mechanism[edit]

Expression of holin S at a precisely scheduled time after phage infection terminates respiration and allows release of a muralytic enzyme, endolysin, that hydrolyzes the cell wall. Point mutations in the S gene that prevent lethality alter TMSs 1 and 2 and the connecting loop. TMS 2 is particularly important for function. A three-step mechanism (monomer → dimer → oligomeric pore) has been proposed for assembly of the pore.[5] S105 (holin) and S107 (inhibitor) form an abortive dimer. Only when S105 production exceeds that of S107 (which occurs at a specific developmental time), do functional holes appear in the bacterial cell membrane.[5] For holin S105, the helix-turn-helix motif in transmembrane domain 3 provides the driving force of dimerization.[6]

Holins regulate the length of the infection cycle of tailed phages (caudovirales) by oligomerizing to form lethal holes in the cytoplasmic membrane at a time dictated by their primary structures. Savva et al. (2008) used electron microscopy and single-particle analysis to characterize structures formed by the bacteriophage lambda holin (S105) in vitro.[7] In non-ionic or mild zwitterionic detergents, purified S105, but not the lysis-defective variant S105A52V, formed rings of at least two size classes, the most common having inner and outer diameters of 8.5 and 23 nm respectively, and containing approximately 72 S105 monomers. The height of these rings, 4 nm, closely matches the thickness of the lipid bilayer. The central channel is of unprecedented size for channels formed by integral membrane proteins, consistent with the non-specific nature of holin-mediated membrane permeabilization. S105, present in detergent-solubilized rings and in inverted membrane vesicles, showed similar sensitivities to proteolysis and cysteine-specific modification, suggesting that the rings are representative of the lethal holes formed by S105 to terminate the infection cycle and initiate lysis.[7]

Homologues[edit]

A homologue of λ holin S from the lysogenic Xenorhabdus nematophila, hol-1 (TC #1.E.2.1.4), has been shown to be a functional holin. When cloned into wild-type E. coli, it causes hemolysis due to the release of the SheA hemolysin.[8] Another holin (phage H-19B holin) is encoded by a gene associated with the Shiga-like toxin I gene of E. coli.[9] Thus, it appears that holins can export various toxins as well as autolysins.

The holes caused by S105 have an average diameter of 340 nm, and some exceeding 1 micron. Most cells exhibit only one irregular hole, randomly positioned in the membrane, irrespective of its size.[10] During λ infection, S105 accumulates harmlessly in the membrane until it forms a single irregular hole, releasing the endolysin from the cytoplasm, resulting in lysis within seconds. Using a functional S105-GFP fusion, it was demonstrated that the protein accumulates uniformly in the membrane, and then within 1 minute, it forms aggregates at the time of lethality. Thus, like bacteriorhodopsin, the protein accumulates until it reaches a critical concentration for nucleation.[11]

See also[edit]

Further reading[edit]

  • Agu, Chukwuma A.; Klein, Reinhard; Lengler, Johannes; Schilcher, Franz; Gregor, Wolfgang; Peterbauer, Thomas; Bläsi, Udo; Salmons, Brian; Günzburg, Walter H. (2007). "Bacteriophage-encoded toxins: the lambda-holin protein causes caspase-independent non-apoptotic cell death of eukaryotic cells". Cellular Microbiology. 9 (7): 1753–1765. doi:10.1111/j.1462-5822.2007.00911.x. PMID 17346308. S2CID 29678720.
  • Barenboim, M.; Chang, C. Y.; Hajj, F.; Young, R. (1999). "Characterization of the dual start motif of a class II holin gene". Molecular Microbiology. 32 (4): 715–727. doi:10.1046/j.1365-2958.1999.01385.x. PMID 10361276. S2CID 27367693.
  • Bläsi, U.; Fraisl, P.; Chang, C. Y.; Zhang, N.; Young, R. (1999). "The C-terminal sequence of the lambda holin constitutes a cytoplasmic regulatory domain". Journal of Bacteriology. 181 (9): 2922–2929. doi:10.1128/jb.181.9.2922-2929.1999. PMC 93738. PMID 10217787.
  • White, Rebecca; Tran, Tram Anh T.; Dankenbring, Chelsey A.; Deaton, John; Young, Ry (2010). "The N-terminal transmembrane domain of lambda S is required for holin but not antiholin function". Journal of Bacteriology. 192 (3): 725–733. doi:10.1128/JB.01263-09. PMC 2812449. PMID 19897658.

References[edit]

  1. ^ Reddy, Bhaskara L.; Saier, Milton H. (2013-11-01). "Topological and phylogenetic analyses of bacterial holin families and superfamilies". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1828 (11): 2654–2671. doi:10.1016/j.bbamem.2013.07.004. ISSN 0006-3002. PMC 3788059. PMID 23856191.
  2. ^ Gründling, A.; Smith, D. L.; Bläsi, U.; Young, R. (2000-11-01). "Dimerization between the holin and holin inhibitor of phage lambda". Journal of Bacteriology. 182 (21): 6075–6081. doi:10.1128/jb.182.21.6075-6081.2000. ISSN 0021-9193. PMC 94741. PMID 11029427.
  3. ^ Gründling, A.; Bläsi, U.; Young, R. (2000-11-01). "Genetic and biochemical analysis of dimer and oligomer interactions of the lambda S holin". Journal of Bacteriology. 182 (21): 6082–6090. doi:10.1128/jb.182.21.6082-6090.2000. ISSN 0021-9193. PMC 94742. PMID 11029428.
  4. ^ Gründling, A.; Bläsi, U.; Young, R. (2000-01-14). "Biochemical and genetic evidence for three transmembrane domains in the class I holin, lambda S". The Journal of Biological Chemistry. 275 (2): 769–776. doi:10.1074/jbc.275.2.769. ISSN 0021-9258. PMID 10625606.
  5. ^ a b Graschopf, A.; Bläsi, U. (1999-07-01). "Functional assembly of the lambda S holin requires periplasmic localization of its N-terminus". Archives of Microbiology. 172 (1): 31–39. Bibcode:1999ArMic.172...31G. doi:10.1007/s002030050736. ISSN 0302-8933. PMID 10398749. S2CID 19482183.
  6. ^ Zhou, Brian; Wu, Yinghao; Su, Zhaoqian (2021-06-29). "Computational Simulation of Holin S105 in Membrane Bilayer and Its Dimerization Through a Helix-Turn-Helix Motif". The Journal of Membrane Biology. 254 (4): 397–407. doi:10.1007/s00232-021-00187-w. ISSN 1432-1424. PMC 10811654. PMID 34189599. S2CID 235688266.
  7. ^ a b Savva, Christos G.; Dewey, Jill S.; Deaton, John; White, Rebecca L.; Struck, Douglas K.; Holzenburg, Andreas; Young, Rye (2008-08-01). "The holin of bacteriophage lambda forms rings with large diameter". Molecular Microbiology. 69 (4): 784–793. doi:10.1111/j.1365-2958.2008.06298.x. ISSN 1365-2958. PMC 6005192. PMID 18788120.
  8. ^ Brillard, Julien; Boyer-Giglio, Marie Hélène; Boemare, Noël; Givaudan, Alain (2003-01-21). "Holin locus characterisation from lysogenic Xenorhabdus nematophila and its involvement in Escherichia coli SheA haemolytic phenotype". FEMS Microbiology Letters. 218 (1): 107–113. doi:10.1016/s0378-1097(02)01139-4. ISSN 0378-1097. PMID 12583905.
  9. ^ Neely, M. N.; Friedman, D. I. (1998-06-01). "Functional and genetic analysis of regulatory regions of coliphage H-19B: location of shiga-like toxin and lysis genes suggest a role for phage functions in toxin release" (PDF). Molecular Microbiology. 28 (6): 1255–1267. doi:10.1046/j.1365-2958.1998.00890.x. hdl:2027.42/74784. ISSN 0950-382X. PMID 9680214. S2CID 1414516.
  10. ^ Dewey, Jill S.; Savva, Christos G.; White, Rebecca L.; Vitha, Stanislav; Holzenburg, Andreas; Young, Ry (2010-02-02). "Micron-scale holes terminate the phage infection cycle". Proceedings of the National Academy of Sciences of the United States of America. 107 (5): 2219–2223. Bibcode:2010PNAS..107.2219D. doi:10.1073/pnas.0914030107. ISSN 1091-6490. PMC 2836697. PMID 20080651.
  11. ^ White, Rebecca; Chiba, Shinobu; Pang, Ting; Dewey, Jill S.; Savva, Christos G.; Holzenburg, Andreas; Pogliano, Kit; Young, Ry (2011-01-11). "Holin triggering in real time". Proceedings of the National Academy of Sciences of the United States of America. 108 (2): 798–803. Bibcode:2011PNAS..108..798W. doi:10.1073/pnas.1011921108. ISSN 1091-6490. PMC 3021014. PMID 21187415.

As of 10 March 2016, this article is derived in whole or in part from Transporter Classification Database (TCDB). The copyright holder has licensed the content in a manner that permits reuse under CC BY-SA 3.0 and GFDL. All relevant terms must be followed. The original text was at "1.E.2 The Lambda Holin S (λ Holin) Family"

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